scholarly journals Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes

2021 ◽  
Author(s):  
Lucile Ben Haim ◽  
Lucas Schirmer ◽  
Amel Zulji ◽  
Khalida Sabeur ◽  
Brice Tiret ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Glutamine Synthetase ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Conditional Knockout ◽  
Oligodendrocyte Progenitor Cells ◽  
Mouse Spinal Cord ◽  
Reporter Mice ◽  
Key Enzyme ◽  
Ventral Spinal Cord

Glutamine synthetase (GS) is a key enzyme that metabolizes glutamate into glutamine. While GS is expressed by astrocytes of the central nervous system (CNS), expression in other glial lineages has been noted. Using a combination of reporter mice and cell type-specific markers, we show that GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells (OPC) of the mouse spinal cord abutting ventral horn motor neurons. To investigate the role of GS in mature OL, we used a conditional knockout (cKO) approach to selectively delete GS-encoding gene (Glul) in OL, which caused a significant decrease in glutamine levels on spinal cord extracts. We evaluated the effect on ventral spinal cord sensorimotor circuits and observed that GS cKO mice (CNP-cre+ : Glul fl/fl) showed no differences in motor neuron numbers, size or axon density; OL differentiation and myelination in the ventral spinal cord at 1- and 6-months of age was normal. Interestingly, GS cKO mice showed an early and specific decrease in peak force while motor function remained otherwise unaffected. These findings provide evidence OL-encoded GS functions in spinal cord sensorimotor circuit.

scholarly journals Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons

2021 ◽  
Vol 24 (4) ◽  
pp. 572-583 ◽  
Author(s):  
Jacob A. Blum ◽  
Sandy Klemm ◽  
Jennifer L. Shadrach ◽  
Kevin A. Guttenplan ◽  
Lisa Nakayama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Single Cell ◽  
Motor Neurons ◽  
Molecular Diversity ◽  
Adult Mouse ◽  
Transcriptomic Analysis ◽  
Mouse Spinal Cord

scholarly journals Diminished ventral oligodendrocyte precursor generation results in the subsequent over-production of dorsal oligodendrocyte precursors of aberrant morphology and function

2020 ◽  
Author(s):  
Lev Starikov ◽  
Andreas H. Kottmann
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Ventricular Zone ◽  
Normal Numbers ◽  
Spinal Cord Development ◽  
Oligodendrocyte Precursor ◽  
And Function ◽  
Sod1 Mouse ◽  
Lateral Sclerosis ◽  
Ventral Spinal Cord

AbstractOligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain at the end of neurogenesis during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here we show that ablating Shh signaling from nascent ventricular zone derivatives and partially from the floor plate results in a severe diminishment of ventral derived OPCs but normal numbers of motor neurons in the postnatal spinal cord. In the absence of ventral vOPCs, dorsal dOPCs populate the entire spinal cord resulting in an increased OPC density in the ventral horns. These OPCs take on an altered morphology, do not participate in the removal of excitatory vGlut1 synapses from injured motor neurons, and exhibit morphological features similar to those found in the vicinity of motor neurons in the SOD1 mouse model of Amyotrophic Lateral Sclerosis (ALS). Our data indicates that vOPCs prevent dOPCs from invading ventral spinal cord laminae and suggests that vOPCs have a unique ability to communicate with injured motor neurons.

scholarly journals Presynaptic Angiotensin II AT1 Receptors Enhance Inhibitory and Excitatory Synaptic Neurotransmission to Motoneurons and Other Ventral Horn Neurons in Neonatal Rat Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1405-1412 ◽  
Author(s):  
Murat Oz ◽  
Keun-Hang Yang ◽  
Michael J. O'Donovan ◽  
Leo P. Renaud
Keyword(s):  
Spinal Cord ◽  
Angiotensin Ii ◽  
Ventral Horn ◽  
Synaptic Activity ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Synaptic Neurotransmission ◽  
Excitatory Neurotransmission ◽  
Ventral Spinal Cord

In neonatal spinal cord, we previously reported that exogenous angiotensin II (ANG II) acts at postsynaptic AT1 receptors to depolarize neonatal rat spinal ventral horn neurons in vitro. This study evaluated an associated increase in synaptic activity. Patch clamp recordings revealed that 38/81 thoracolumbar (T7–L5) motoneurons responded to bath applied ANG II (0.3–1 μM; 30 s) with a prolonged (5–10 min) and reversible increase in spontaneous postsynaptic activity, selectively blockable with Losartan ( n = 5) but not PD123319 ( n = 5). ANG-II-induced events included both spontaneous inhibitory (IPSCs; n = 6) and excitatory postsynaptic currents (EPSCs; n = 5). While most ANG induced events were tetrodotoxin-sensitive, ANG induced a significant tetrodotoxin-resistant increase in frequency but not amplitude of miniature IPSCs ( n = 7/13 cells) and EPSCs ( n = 2/7 cells). In 35/77 unidentified neurons, ANG II also induced a tetrodotoxin-sensitive and prolonged increase in their spontaneous synaptic activity that featured both IPSCs ( n = 5) and EPSCs ( n = 4) when tested in the presence of selective amino acid receptor antagonists. When tested in the presence of tetrodotoxin, ANG II was noted to induce a significant increase in the frequency but not the amplitude of mIPSCs ( n = 9) and mEPSCs ( n = 8). ANG also increased spontaneous motor activity from isolated mouse lumbar ventral rootlets. Collectively, these observations support the existence of a wide pre- and postsynaptic distribution of ANG II AT1 receptors in neonatal ventral spinal cord that are capable of influencing both inhibitory and excitatory neurotransmission.

scholarly journals Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection

2019 ◽  
Vol 33 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Kazu Kobayakawa ◽  
Kyleigh Alexis DePetro ◽  
Hui Zhong ◽  
Bau Pham ◽  
Masamitsu Hara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
Locomotor Training ◽  
Synaptic Structure ◽  
Cord Injury ◽  
Lumbar Spinal ◽  
Spinal Cord Hemisection ◽  
Activity Dependent

Background. We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. Methods. In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. Results. Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. Conclusions. Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.

scholarly journals Sulfatase 2 Modulates Fate Change from Motor Neurons to Oligodendrocyte Precursor Cells through Coordinated Regulation of Shh Signaling with Sulfatase 1

2017 ◽  
Vol 39 (5) ◽  
pp. 361-374 ◽  
Author(s):  
Wen Jiang ◽  
Yugo Ishino ◽  
Hirokazu Hashimoto ◽  
Kazuko Keino-Masu ◽  
Masayuki Masu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Expression Pattern ◽  
Motor Neurons ◽  
Expression Patterns ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Shh Signaling ◽  
Sulfatase Activity ◽  
Oligodendrocyte Precursor ◽  
Ventral Spinal Cord

Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2, which specifically remove sulfate from heparan sulfate proteoglycans. Although several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh) signaling during embryonic ventral spinal cord development, the detailed expression pattern and function of Sulf2 in the spinal cord remains to be determined. In this study, we found that Sulf2 also modulates the cell fate change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1. In the mouse, Sulf mRNAs colocalize with Shh mRNA and gradually expand dorsally from embryonic day (E) 10.5 to E12.5, following strong Patched1 signals (a target gene of Shh signaling). This coordinated expression pattern led us to hypothesize that in the mouse, strong Shh signaling is induced when Shh is released by Sulf1/2, and this strong Shh signaling subsequently induces the dorsal expansion of Shh and Sulf1/2 expression. Consistent with this hypothesis, in the ventral spinal cord of Sulf1 knockout (KO) or Sulf2 KO mice, the expression patterns of Shh and Patched1 differed from that in wild-type mice. Moreover, the position of the pMN and p3 domains were shifted ventrally, MN generation was prolonged, and OPC generation was delayed at E12.5 in both Sulf1 KO and Sulf2 KO mice. These results demonstrated that in addition to Sulf1, Sulf2 also plays an important and overlapping role in the MN-to-OPC fate change by regulating Shh signaling in the ventral spinal cord. However, neither Sulf1 nor Sulf2 could compensate for the loss of the other in the developing mouse spinal cord. In vitro studies showed no evidence of an interaction between Sulf1 and Sulf2 that could increase sulfatase activity. Furthermore, Sulf1/2 double heterozygote and Sulf1/2 double KO mice exhibited phenotypes similar to the Sulf1 KO and Sulf2 KO mice. These results indicate that there is a threshold for sulfatase activity (which is likely reflected in the dose of Shh) required to induce the MN-to-OPC fate change, and Shh signaling requires the coordinated activity of Sulf1 and Sulf2 in order to reach that threshold in the mouse ventral spinal cord.

scholarly journals ERG Conductance Expression Modulates the Excitability of Ventral Horn GABAergic Interneurons That Control Rhythmic Oscillations in the Developing Mouse Spinal Cord

2007 ◽  
Vol 27 (4) ◽  
pp. 919-928 ◽  
Author(s):  
F. Furlan ◽  
G. Taccola ◽  
M. Grandolfo ◽  
L. Guasti ◽  
A. Arcangeli ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ventral Horn ◽  
Gabaergic Interneurons ◽  
Mouse Spinal Cord

scholarly journals Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives

Development ◽  
2021 ◽  
Vol 148 (6) ◽  
Author(s):  
Matthew Wind ◽  
Antigoni Gogolou ◽  
Ichcha Manipur ◽  
Ilaria Granata ◽  
Larissa Butler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Lumbosacral Spinal Cord ◽  
Bona Fide ◽  
Promising Solution ◽  
Bmp Signalling ◽  
Crucial Parameter ◽  
Ventral Spinal Cord

ABSTRACT The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFβ-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities.

scholarly journals Fully Characterized Mature Human iPS- and NMP-Derived Motor Neurons Thrive Without Neuroprotection in the Spinal Contusion Cavity

2022 ◽  
Vol 15 ◽  
Author(s):  
Zachary T. Olmsted ◽  
Cinzia Stigliano ◽  
Brandon Marzullo ◽  
Jose Cibelli ◽  
Philip J. Horner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Motor Neurons ◽  
Ex Vivo ◽  
Cervical Spinal Cord ◽  
Neural Cell ◽  
Oligodendrocyte Progenitor Cells ◽  
Limited Information ◽  
Cord Injury

Neural cell interventions in spinal cord injury (SCI) have focused predominantly on transplanted multipotent neural stem/progenitor cells (NSPCs) for animal research and clinical use due to limited information on survival of spinal neurons. However, transplanted NSPC fate is unpredictable and largely governed by injury-derived matrix and cytokine factors that are often gliogenic and inflammatory. Here, using a rat cervical hemicontusion model, we evaluate the survival and integration of hiPSC-derived spinal motor neurons (SMNs) and oligodendrocyte progenitor cells (OPCs). SMNs and OPCs were differentiated in vitro through a neuromesodermal progenitor stage to mimic the natural origin of the spinal cord. We demonstrate robust survival and engraftment without additional injury site modifiers or neuroprotective biomaterials. Ex vivo differentiated neurons achieve cervical spinal cord matched transcriptomic and proteomic profiles, meeting functional electrophysiology parameters prior to transplantation. These data establish an approach for ex vivo developmentally accurate neuronal fate specification and subsequent transplantation for a more streamlined and predictable outcome in neural cell-based therapies of SCI.

Autologous adipose-derived stem cells attenuate muscular atrophy and protect spinal cord ventral horn motor neurons in an animal model of burn injury

Cytotherapy ◽  
2015 ◽  
Vol 17 (8) ◽  
pp. 1066-1075 ◽  
Author(s):  
Sheng-Hua Wu ◽  
Shu-Hung Huang ◽  
Yi-Ching Lo ◽  
Chee-Yin Chai ◽  
Su-Shin Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Animal Model ◽  
Motor Neurons ◽  
Burn Injury ◽  
Muscular Atrophy ◽  
Ventral Horn ◽  
Adipose Derived Stem Cells
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